Molecular Toxicology

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Human molecular toxicology studies the molecular mechanisms underlying toxicity of compounds in man. The conversion to reactive intermediates and metabolites is key in the actual toxicity of compounds. Therefore, the role of metabolism in the formation of metabolites and reactive intermediates and the protection against these species is extensively addressed. Moreover, compounds generally display a toxicity that is restricted to a specific organ and type of toxicity. This concept of selective toxicity is elaborated. Focus is on redox-controlled processes in biotransformation and in modulation of cell function. Topics include a survey of the molecular mechanisms determining (selective) toxicity; the versatility of enzymes, such as cytochrome P450 and glutathione S- transferases in the biotranformation of compounds; consequences of genetic polymorphisms of biotransformation enzymes; chemical and biological properties of various classes of reactive intermediates; structure-activity relationships and other approaches applied to predict metabolism; and strategies to reduce toxicity.